The proposed studies aim to investigate mechanisms determining the proportions at which a steroid hormone formed in the syncytiotrophoblast is secreted into the fetal and maternal circulations. Studies in Rhesus monkeys have shown that estradiol (E2) is preferentially secreted towards the mother whereas estrone (E1) is secreted in approximately equal amounts towards the mother and the fetus. A similar discrepancy in the output of E1 and E2 was observed during preliminary studies in which a cotyledon of a human term placenta was perfused with tritiated androstenedione (A) or testosterone (T), which served as precursors of estrogens in the syncytium. It was also found that addition of ethynylestradiol or an excess of estrogen precursor to the perfusion medium eliminates the selectivity of discharge of E2 towards the maternal perfusate. In planned experiments, these results will be further documented, placing emphasis on the quantitative aspects of the conversion of precursors to metabolites. The existence of E2-specific transport systems in the syncytium will be investigated by studying specific binding of E2 in placental tissue after labeling particulate preparations with 3H-E2 under exchange conditions. Analysis of the preferred direction of output during placental perfusion will be extended to studies of estriol, using 3H-16Alpha dehydroepiandrosterone as a precursor, of A and T, during perfusions of 3H- dehydroepiandrosterone, and of progesterone derived from 3H-20Alpha dihydroprogesterone. Influences that additions of proteins to the perfusion buffer and changes in flow rates may have on the distribution of the output of steroids between the "fetl" and "maternal" perfusates will also be evaluated.